1. Field of the Invention
The present invention relates to a method and an apparatus for screening for reproductive tract inflammation and preeclampsia. More particularly, this invention concerns the method and apparatus for screening for reproductive tract inflammation and preeclampsia which utilize the presence of neutrophil defensins found in bodily fluids and tissues of a patient to indicate that the patient is at risk of having reproductive tract inflammation or preeclampsia.
2. Description of Related Art
Detection of reproductive tract inflammation and preeclampsia may be divided into two categories: diagnosis and screening. Diagnosis is a method of establishing the presence of a particular disease in a patient. Limitations of the current diagnostic methods include the high cost of a medical professional performing an invasive examination to take samples, run tests and analyze results as well as the inefficient utilization of the sensitive, yet expensive, diagnostic tests. For example, when polymerase chain reaction testing and ligase chain reaction testing, two standard diagnostic tests for sexually transmitted diseases, are performed, the medical professional must administer the test which results in an average of ten patients testing negative for every one patient that tests positive.
Optimally, a diagnostic test is employed only after a screening test indicates that the patient is at risk of having a disease in order to eliminate the unnecessary cost of expensive diagnostic tests. Screening is a method of establishing the absence of a particular disease or class of diseases in a patient. When a screening test indicates that a patient does not have a disease, in many cases the need for further diagnostic testing is eliminated. Such screening saves money for patients, health insurance companies and government health programs. In addition, screening provides a way for patients to avoid the discomfort associated with more invasive diagnostic procedures. The following are some of the conventional screening and diagnostic methods used to detect female reproductive tract inflammation and preeclampsia wherein the female reproductive tract inflammation include, but are not limited to, intraamniotic infection, pelvic inflammatory diseases and sexually transmitted diseases such as gonorrhea, chlamydia and trichomoniasis.
Pelvic inflammatory diseases may be caused by anaerobic bacterial infection, allergic reactions or prior infection by a sexually transmitted disease. In general the majority of pelvic inflammatory diseases are not symptomatic and therefore, go undetected. If undetected and untreated, pelvic inflammatory diseases may result in tubal factor infertility. Screening for upper reproductive tract inflammation such as salpingitis, cervicitis, endometritis and oophoritis generally includes a pelvic exam conducted by a physician. If manipulation of the cervix and palpitation of the adnexa produces severe pain during the pelvic exam, the patient is considered to be at risk for pelvic inflammatory disease. A diagnosis of pelvic inflammatory disease may be obtained by performing an endometrial biopsy or operative laparoscopy both of which are highly invasive and uncomfortable procedures conducted by a physician.
Intraamniotic infection is an infection of the amnion or amniotic fluid by any pathogen, and is thought to be a significant cause of idiopathic preterm labor which results in preterm deliveries. Screening for intraamniotic infection involves identifying patients in preterm labor. The standard diagnostic test for intraamniotic infection involves amniocentesis and growing a culture from the extracted amniotic fluid. Because a culture must be grown, diagnosis may take several days and is expensive. Further, diagnosis is often negative in cases where there is significant placental infection or inflammation.
Preeclampsia, an endothelial cell disorder of unknown etiology, occurs in five to seven percent (5-7%) of pregnant women. If undetected and untreated the condition may lead to stillbirth, premature birth, eclampsia or maternal death. The diagnosis of preeclampsia is based on the triad of hypertension, proteinuria and edema. The only known treatment for preeclampsia is delivery of the infant. This is unfortunate because many women with preeclampsia are preterm thereby requiring delivery of a premature infant having the potential for serious neonatal sequelae. Optimally, screening methods to identify those destined to develop preeclampsia would help to study potential treatments aimed at preventing disease manifestations.
The typical screening method for sexually transmitted diseases comprises identifying patients having dysuria and abnormal discharge and the medical practitioner observing whether there is redness, swelling or sores in the genitalia. Additional screening methods include using the leukocyte esterase dipstick or neutrophil quantification on gram chain. Unfortunately these methods have sub-optimal sensitivities and specificities.
Several diagnostic tests for detecting sexually transmitted diseases are readily available in the United States of America and other developed nations. The most accurate diagnostic techniques are polymerase chain reaction and ligase chain reaction which amplify the amount of pathogenic microbial DNA in a patient specimen to detectable levels. Limitations of polymerase chain reaction and ligase chain reaction are the high cost of a medical professional to obtain a specimen from the patient and analyze the results as well as a need for a qualified facility to perform the necessary lab work.
The World Health Organization and some Third World countries use an algorithm comprising a series of questions to screen for sexually transmitted diseases. Because this screening method is based solely on the answers to the questions and not based on a physical assessment of the patient, the degree of error may be high. Further, because of the scarcity of resources in Third World countries, a precise diagnostic test is not performed in cases where the results of the algorithm do not suggest infection thereby missing many patients who truly are infected.
Gonorrhea is caused by the gonococcal bacterium Neisseria gonorrhea. If undetected and untreated, gonorrhea can cause postgonococcal nonspecific urethritis, epididymitis, pelvic inflammatory disease, arthritis and possibly death. One method for diagnosing gonorrhea involves taking a scraping from a patient and performing a Gram-stained smear on the scraping. A culture is required for females because the Gram-stain test for gonorrhea is considered less reliable for females. The disadvantage of this detection method is that it is time consuming and costly because it requires a physician to administer the test.
Chlamydia is caused by the bacterium Chlamydia trachomatous. If undetected and untreated, chlamydia can cause pelvic inflammatory disease, infertility, ectopic pregnancy and chronic pelvic pain. In addition, undetected chlamydia is thought to cause about fifty percent (50%) of the nonspecific sexually transmitted infections, including nongonococcal urethritis and nonspecific urethritis. A standard method for diagnosing chlamydia involves taking a scraping from a patient which in women, is obtained from the endocervix. The specimen is then placed in a sterile nutritive medium and observed under a microscope for signs of microbial growth and the disease organism. Limitations of this diagnostic method include prolonged incubation, cost and sensitivity of only seventy-five percent (75%) to eighty-five percent (85%).
The scraping may also be subject to antigen detection tests, such as direct fluorescent antibody testing (DFA) and enzyme-linked immunosorbent assay (ELISA) to detect the pathogenic microbial proteins. However, because these methods depend on the presence of antigen, the scraping must include microbial cellular material. Other antigen detection methods for the diagnosis of chlamydia include serological tests involving either complement fixation or microimmunofluorescence. Though antigen detection tests for chlamydia are easily performed and are less costly than cultures however, they have lower sensitivities than cultures and low positive predictive values in low prevalence populations.
Trichomoniasis is caused by the flagellate protozoan Trichomonas vaginalis. If undetected and untreated trichomoniasis can cause vaginitis, urethritis, cystitis and prostatitis. The current gold standard for the diagnosis of trichomoniasis is culture on a specimen from the posterior fornix. Although highly sensitive, laboratory availability is limited; therefore, wet mount microscopy conducted on a similar specimen from the posterior fornix is most often used to diagnose this condition. The disadvantage of using this diagnostic test to detect trichomoniasis is that it has a sensitivity of only about fifty percent (50%).
Newer techniques for detecting Neisseria gonorrhoea, Chlamydia trachomatous and Trichomonas vaginalis rely on nucleic acid amplification with subsequent detection. These methods are termed polymerase chain reaction and ligase chain reaction and are considered the most accurate diagnostic methods available. Although commercially available for Chlamydia trachomatous they will soon be available for Neisseria gonorrhoea and are under development for Trichomonas vaginalis. One important aspect of these methods is there reliance only on the presence of a small amount of organism and not in the viability of the organism. This makes it possible for the patient to self-collect a specimen such as urine and/or a swab from the vaginal introitus. Further, as viability is not required a patient can collect the sample and may mail it or delivery it to a reference lab with no decrease in testing sensitivity. The major drawback of these testing methods is the increased cost.
Limitations of the above-noted methods of screening and diagnosing female reproductive tract infections and preeclampsia include inaccuracy, invasiveness, delay between the performance of the test and receipt of the results and need for a medical practitioner to perform the screening or diagnostic tests which results in high cost. Nowhere in the related art is there disclosed or suggested a method and an apparatus for screening for female reproductive tract inflammation and preeclampsia which is inexpensive while being accurate. Therefore, there is a definite need for a method and apparatus for screening for female reproductive tract inflammation and preeclampsia which is inexpensive and effective in order that the general population be tested for these diseases resulting in the diseases being accurately and effectively detected and the patient being treated.
Studies have shown that neutrophil defensins are elevated in blood plasma in patients with either bacterial meningitis or septicemia. This type of method is described in greater detail in Journal of Laboratory Clinical Medicine; volume 122 at pp 202-7 (1993). However, the method of detecting female reproductive tract inflammation and preeclampsia disclosed in the present invention which uses the presence of neutrophil defensins found in bodily fluids and tissues such as vaginal fluids or amniotic fluids has never been disclosed or suggested.